Each motoneuron drives the muscle fibers it innervates in a one-to-one fashion, thus forming a motor unit. Because muscle fiber action potentials are relatively easy to measure, motoneurons are the only CNS cells whose firing patterns can be readily quantified in human subjects. Thus, the motoneuron potentially provides a unique window on CNS function in both normal and disease states. The cellular mechanisms that drive motoneuron firing patterns, however, can only be measured via intracellular studies in animal preparations. Thus, the design of our meeting is inherently cross-disciplinary: to bring together specialists investigating motor unit firing patterns in human subjects with specialists focusing on cellular mechanisms underlying motoneuron electrical behavior. To facilitate interactions between labs, each session consists of an introduction for non-specialists, short presentations, and extended time for discussion. Each session will have at least one presentation by a post-doctoral fellow or a graduate student. The meeting will begin with cellular presentations and proceed to human data, with the transition focusing on recent developments in high speed, biologically realistic computer simulations that potentially provide a platform for quantitatively relating these two types of data. The issue at the heart of the meeting is, to what degree the present state-of-the- art results and simulations allow identification of the cellular mechanisms of plastic changes that take place in motor unit firing patterns both in normal function (fatigue, exercise) and in disease states (spinal injury, hemiparetic stroke, and ALS). The meeting will end with an entire session devoted to discussion of this fundamental question. The abstracts submitted by each invited speaker will be posted on a publicized website. We anticipate that this meeting will generate new ideas and approaches for investigation of plasticity in the motor system as well as creation of new therapeutic strategies for spasticity in spinal injury and stroke and motoneuron degeneration in ALS. PUBLIC HEALTH RELEVANCE: This application seeks support for international meeting on mechanisms of plasticity and disease in motoneurons. The 3.5 day conference will bring together specialists investigating motor unit firing patterns in human subjects with specialists focusing on cellular mechanisms underlying motoneuron electrical behavior. [unreadable] [unreadable] [unreadable]